Pulmonary Artery Pulsatility Index Predicts Mechanical Circulatory Support Following Heart Transplantation

The incidence of MCS for early graft dysfunction (EGD) following heart transplantation varies from 2.3% - 28.2%. Low pulmonary pulsatility index (PAPi) is associated with higher mortality in advanced heart failure and cardiogenic shock. We hypothesised that a lower pulmonary pulsatility index following heart transplantation is associated with MCS use for EGD. Methods Two-centre study of consecutive heart transplantation from May 2018 to December 2022. Haemodynamic parameters and Inotropic/Vasoconstrictor data were investigated on admission to intensive care unit (T0) and at six hours later (T6). Results Of the 173 patients included in this study, 24 had MCS for EGD. PAPi in the group that required MCS were lower at T0 (1.21(0.84) vs 1.67(1.23), p=0.001) and T6 (0.77(0.52) vs 1.44(0.82), p=<0.001). There was no significant difference in recipient characteristics, donor characteristics (donor age and sex matching) and operative factors (warm/cold ischaemic time, total ischaemic time, cardiopulmonary bypass time) between the two groups. On multiple variable regression, PAPi at T6 was associated with delayed MCS independent of total donor organ ischaemic time and short term MCS bridge to transplantation (OR 0.1 (0.036-0.276), p= <0.001). ROC analysis showed an AUC of 0.694 for T0 PAPi and 0.832 for T6 PAPi; a cut-off T6 PAPi of 1.22 had sensitivity and specificity of 81% and 65% respectively.Conclusions Lower PAPi at T6 (<1.22) is independently associated with MCS use for severe EGD post-heart transplantation

Geographical Variation in the Response of Visceral Leishmaniasis to Paromomycin in East Africa: A Multicentre, Open-Label, Randomized Trial

Visceral leishmaniasis (VL) is a fatal parasitic disease with 500,000 new cases each year according to WHO estimates. New and better treatment options are urgently needed in disease endemic areas due to the long courses, toxicity and development of resistance to current treatments. Recently, the antibiotic paromomycin was tested and registered in India to treat this disease. The current study describes a clinical trial to test the effectiveness of injectable paromomycin, either alone or in combination with the standard drug sodium stibogluconate in three East African countries—Sudan, Kenya and Ethiopia. The study showed that at the same paromomycin dose that was successfully used and registered in India, a far poorer outcome was obtained, particularly in Sudan, suggesting that there are either differences in the patients ability to respond to the drug or in the susceptibility of parasites in East Africa compared with those in India. However, no major safety concerns were noted with the treatment. Further research was initiated to see if a higher dose of paromomycin would perform better, especially in Sudan. The results of this and the performance of the combination arm will be reported later. Our study highlights the importance of considering geographical differences to treatment responses

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

A Case of Bacteremia and Meningitis Associated with Piperacillin-Tazobactam Nonsusceptible, Ceftriaxone Susceptible Escherichia coli during Strongyloides Hyperinfection in an Immunocompromised Host

Strongyloidiasis is an emerging parasitic infection with intriguing epidemiology, presentation, and clinical management. We report a case of hyperinfection syndrome complicated by E. coli bacteremia and meningitis with one of the isolates showing a unique resistance pattern recently being recognized. This report describes the aspect of invasive bacterial infections in strongyloidiasis and highlights the unique susceptibility pattern of the E. coli isolate and the extreme caution required during the antibiotic therapy

Unresponsiveness to AmBisome in some Sudanese patients with kala-azar.

In Sudan, two treatments are currently registered for visceral leishmaniasis: sodium stibogluconate (SSG) as first line and liposomal amphotericin B (AmBisome) as second line. We present 64 patients (52 relapse cases to SSG, 12 new but complicated cases) treated with AmBisome in eastern Sudan. AmBisome was administered at 2.5-8.2mg/kg (15-49mg/kg in total) per dose six times (days 1, 2, 3, 5, 10, 15) as an intravenous infusion. We measured outcome according to clinical response and parasitological clearance (lymph node aspiration). Patient outcomes fell into three groups: group 1, clinical responders (cured) with a negative test of cure (n=35); group 2, clinical responders with a positive test of cure (n=19); group 3, clinical non-responders (failures) with a positive test of cure (n=10). Of the 10 failures, six were already relapse cases. All of group 3, and 15 from group 2, were also treated with additional SSG (20mg/kg intramuscularly daily for 30-50 d) with resulting clinical and parasitological improvement. Parasite persistence and clinical failure were associated with a higher parasite density on admission (P<0.002) and underlying immunosuppressive disease: tuberculosis (three cases) or HIV (two cases). Because AmBisome monotherapy may fail in Sudan, a combination of AmBisome and SSG is recommended for relapse cases